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Vortioxetine (Trintellix)

Multimodal antidepressant • Last reviewed 2025-09-26

General information

Vortioxetine is a multimodal antidepressant indicated for major depressive disorder. Its combined serotonin reuptake inhibition and receptor modulation aim to improve cognition and reduce sexual side effects relative to traditional SSRIs.

Tablets (5, 10, 20 mg) are taken once daily without regard to meals. Cognitive improvements and low rates of weight gain or sexual dysfunction differentiate vortioxetine in comparative trials.

Because the half-life is ~66 hours, vortioxetine tolerates missed doses reasonably well but requires dosage adjustments with strong CYP2D6 inhibitors or in poor metabolizers.

Common adverse effects include nausea and vomiting, usually transient within 1–2 weeks.

Dosing & administration

Start 10 mg once daily; increase to 20 mg as tolerated after 1–2 weeks.

Reduce to 5 mg when co-administered with strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion).

Taper to 10 mg for 1 week before stopping to minimize discontinuation symptoms.

Mechanism of action

Inhibits the serotonin transporter and modulates 5-HT receptors: agonist at 5-HT1A, partial agonist at 5-HT1B, antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors.

Metabolism & pharmacokinetics

Absolute bioavailability ~75%; peak plasma concentrations occur ~7 hours post-dose. Metabolized hepatically mainly via CYP2D6, with contributions from CYP3A4 and CYP2C19. Elimination half-life ~66 hours; steady state in ~2 weeks.

Drug interactions

Avoid MAOIs, linezolid, or IV methylene blue (serotonin syndrome).

Reduce dose when combined with strong CYP2D6 inhibitors.

CYP inducers (rifampin, carbamazepine) may lower exposure; consider higher dose or alternative.

Monitoring & safety checks

Discontinuation guidance

Due to long half-life, tapering may be abbreviated (e.g., 10 mg daily for 1 week). Monitor for mild withdrawal symptoms such as headache or dizziness.

References

  1. Trintellix (vortioxetine) prescribing information — DailyMed (2024)
  2. Vortioxetine for major depressive disorder — Journal of Psychopharmacology (2018)
  3. APA Depression Guideline 2023 (2023)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.